Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.

BACKGROUND: A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles. RESULTS: One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups. CONCLUSIONS: We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.

Cisplatin and vinorelbine as neoadjuvant chemotherapy in locally advanced cervical cancer: a phase II study.

Fifty eight consecutive untreated patients with locally advanced cervical carcinoma (LACC) received neoadjuvant chemotherapy (NACT) with cisplatin (CDDP) 80 mg/sqm (day 1) + vinorelbine (VRL) 25 mg/sqm (day 1 and 8). Three cycles of chemotherapy were planned every 21 days. Within 28 days from the completion of chemotherapy patients in complete or partial response were submitted to radical hysterectomy with pelvic lymphadenectomy. On 155 cycles, hematologic toxicity was mild (G3-4 neutropenia and anemia occurred in 16% and 5%, respectively). Forty-seven patients (81%) were submitted to radical surgery; eight (14%) patients were deemed ineligible for surgery because of poor response to treatment, two (3%) for anesthesia contraindications and one (2%) refused surgery. At pathologic examination 12 patients (25%) had a complete response, one (2%) in-situ carcinoma, six (13%) residual microinvasive disease, and 28 (60%) a partial response. None had extracervical disease. Eight patients (14%) had microscopic lymph node metastases. The number of cycles administered was significantly associated with a good pathologic response. Association of CDDP and VRL as NACT in LACC appears safe and effective. Low cost and modest toxicity would support the initiation of a multicenter randomized phase III trial to compare this association with cisplatin alone.

Ovarian carcinoma metastatic to the breast.

Breast involvement in ovarian cancer is extremely rare. We report a case of solitary breast metastasis from ovarian carcinoma in a 43-year-old white woman, 3 months following diagnosis of ovarian cancer. The diagnostic, therapeutic and prognostic aspects as well as a review of the literature of this uncommon site of metastasis are discussed.

Intramedullary spinal cord metastasis from ovarian carcinoma.

BACKGROUND: Intramedullary spinal cord involvement by ovarian carcinoma is extremely rare. CASE: A patient with stage IV serous cystadenocarcinoma of the ovary presented with neurologic complaints 16 months after primary treatment. Magnetic resonance imaging demonstrated a metastatic lesion in the intramedullary area of the spinal cord. No other site of metastatic disease was observed. The patient received three cycles of carboplatin with complete resolution of the neurologic symptoms and a remarkable reduction of the lesion. Following chemotherapy she was given radiotherapy on the spinal cord, but died 10 months later for disseminated abdominal disease, without neurologic symptoms. CONCLUSION: Spinal cord involvement is unusual in ovarian carcinoma; multidisciplinary treatment, including chemotherapy and radiotherapy, may offer good palliation of the symptomatology.

Large-cell variant of small cell carcinoma of the ovary with hypercalcaemia.

A rare case of large-cell variant of hypercalcemic small cell carcinoma of the ovary diagnosed in a 17 year-old girl is presented and discussed. The patient died of disease progression and severe hypercalcemia within 25 months of diagnosis.

Primary peritoneal carcinoma: a report of twelve cases and a review of the literature.

Primary peritoneal carcinoma (PPC) is rare tumor histologically identical to epithelial ovarian carcinoma (EOC); it is differentiated from EOC based on the extent of gross ovarian involvement and microscopic invasion of the cortex. We report 12 cases of PPC which were diagnosed in our Department during a 9-year period. Total abdominal hysterectomy, bilateral salpingo-oophorectomy and omentectomy were performed in 9 patients, while 3 underwent only explorative laparotomy with bilateral salpingo-oophorectomy. All patients were treated with postoperative platinum-based chemotherapy. After a median follow-up of 42 months, only 5 patients are alive without disease. PPC is a rare tumor currently managed in the same way as ovarian cancer. Primary debulking surgery and chemotherapy represent the cornerstones of treatment. Considering the limited number of patients with PPC, no definitive conclusion can be drawn concerning the prognostic factors for survival.

[Reconstructive surgery in oncological gynecology. Our experience]. / La chirurgia ricostruttiva in ginecologia oncologica. Nostra esperienza.

BACKGROUND: Personal experience in reconstructive surgery for gynecologic oncology is reported. These techniques are playing, during last years, a leading role since it is necessary to assure a good treatment and top quality lifestyle to oncologic patients. METHODS: A retrospective study was made on 357 major surgical treatments for neoplastic disease at the IInd Clinic of Obstetrics and Gynecology, University of Bari. For each disease the technique, the length of surgery and possible complications have been reported. In total 50 reconstructive procedures on 357 surgical interventions for gynecologic neoplastic disease (14%) were made. RESULTS: There was no rate of mortality, and the complications were found only in 5 patients (10%). CONCLUSIONS: Reconstructive surgery can increase surgical radicality, improve the quality of life of the patients and reduce the postoperative complications.

[Combination of cisplatin and vinorelbin in the neoadjuvant treatment of locally advanced cervical carcinoma. Phase II study]. / Associazione di cisplatino e vinorelbina nel trattamento neoadiuvante del cancro cervicale localmente avanzato. Studio di fase II.

BACKGROUND: Aim of this phase II study is to evaluate the cytoreductive efficacy and the toxicity of a regimen consisting of cisplatin and vinorelbine as neoadjuvant chemotherapy for three cycles every 21 days in patients with locally-advanced cervical carcinoma. METHODS: Between April 1996 and December 1998, 33 untreated patients with locally-advanced cervical carcinoma received neoadjuvant chemotherapy with cisplantino 80 mg/m2 (day 1) plus vinorelbine 25 mg/m2 (day 1 and 8). Within 28 days from completion of chemotherapy patients in complete or partial response were submitted to radical hysterectomy plus pelvic lymphadenectomy. RESULTS: Twenty-six patients (79%) were submitted to radical surgery; four patients were not submitted to surgery because of poor response to treatment, two for anesthesiological contraindications and one refused surgery. The combination of cisplatin plus vinorelbine in this phase II study induced a clinical overall response rate of 90%, with 8 pathologic complete response (24%). CONCLUSIONS: The association of cisplatin and vinorelbine as neoadjuvant chemotherapy in locally-advanced cervical carcinoma showed to be safe and effective with a low cost and poor toxicity.

Splenic involvement in ovarian cancer. Description of three cases.

Metastatic involvement of the spleen in patients with ovarian cancer is unusual. Solitary splenic metastasis in the absence of disseminated disease are rare. Three cases of advanced ovarian cancer with splenic involvement are reported. The splenectomy was adopted in two patients.

Surgical decompression and radiation therapy in epidural metastasis from cervical cancer.

Spinal cord compression by epidural metastasis is considered an exceptional complication in patients with cervical carcinoma. We report three patients treated for a cervical carcinoma who developed epidural metastasis with spinal cord compression at 9, 25 and 48 months after primary treatment of the uterine malignancy. All patients had poorly-differentiated adenocarcinomas with lymphovascular space invasion, and two had lymph node metastasis. All patients underwent emergency decompressive laminectomy followed by radiotherapy and a partial recovery of the neurological function was achieved. In two patients the spinal cord was the only site of recurrent disease, whereas the other had lung and brain metastasis at the time of epidural involvement diagnosis. All three patients, however, died of disseminated disease. Surgical decompression followed by radiation therapy may result in a complete preservation of the neurologic functions in patients with spinal cord compression secondary to metastatic carcinoma of the uterine cervix. Considering the propensity for disseminated disease, long term survival might be achieved only with the use of effective chemotherapy.

Prognostic factors and selective use of vaginal hysterectomy in early stage endometrial carcinoma.

INTRODUCTION: Endometrial cancer represents the fourth most frequent malignancy in women of any age, tending to become the most common gynaecological tumor in developed Countries. A retrospective analysis has been conducted on the prognostic factors of endometrial neoplasm during 15-years experience (1977-1991). MATERIAL AND METHODS: 321 patients affected by stage I and II endometrial carcinoma have been treated surgically first hand. Surgical-pathological staging and prognostic factors were reviewed and related to follow-up and 5-year survival rate. RESULTS: The age-peak of patients was 50-70 years; prevalent histologic type was adenocarcinoma (95.6%); 269 patients were in stage I and 52 in stage II. In stage I disease overall 5-year survival rate resulted to be 81.4%, while in stage II it fell to 59.6%. DISCUSSION: Myometrial involvement by adenocarcinomatous cells is probably the most important prognostic factor, considering its reliability and non-contradictory evaluation. Our data confirm there is no difference in impact on 5-year survival between abdominal and vaginal routes in clinical stage I and occult stage II endometrial carcinoma.

Primary non Hodgkin's lymphoma of the vagina.

The genital tract as a primary site of malignant lymphoma in women is extremely rare. This report concerns a 64 year old patient with a primary vaginal non-Hodgkin lymphoma (large cell B lineage according to the REAL classification--centroblastic type according to the Kiel classification--"G" according Working Formulation) with an unusual clinical presentation--pelvic discomfort accompanied by frequent ureteral-like colic. Due to gynecological onset symptoms and the rarity of this extranodal primary site misinterpretation of a primary vaginal lymphoma as a benign inflammatory disease or endometriosis may occur. We emphasize the importance of their recognition and also the differential diagnosis of cervical lymphoma from other neoplastic and non-neoplastic lesions.

Surgical treatment of recurrent ovarian cancer: report of 21 cases and a review of the literature.

AIM: To evaluate the role of secondary cytoreductive surgery in patients with recurrent ovarian cancer. PATIENTS AND METHODS: A retrospective chart review was conducted on 21 patients submitted to secondary cytoreductive surgery for apparently isolated and resectable recurrence of ovarian cancer, after a disease-free interval of at least 12 months. RESULTS: Fifteen patients (71%) had complete surgical debulking with no macroscopic tumor at the completion of the surgical procedure. Eight patients (38%) required an intestinal resection but no colostomy was performed. Eleven complications were recorded in nine patients, but no operative death occurred. The median survival time for all patients after diagnosis of recurrent disease was 29 months (range 6-96 months). Survival time after diagnosis of recurrence was not significantly related either to known prognostic factors of ovarian cancer or to the length of the clinical remission time. The absence of residual disease after salvage surgery was the only factory associated with prolonged survival. CONCLUSION: Secondary cytoreductive surgery is a safe procedure which should be offered to recurrent ovarian cancer patients with apparently isolated and resectable disease, and without ascitis.

Endometrial stromal sarcoma: a clinicopathologic study.

BACKGROUND: This study is a clinicopathologic evaluation of five patients with endometrial stromal sarcoma. PATIENTS AND METHODS: Over a period of 9 years 5 cases of ESS were observed in our Unit. The patients were retrospectively staged according to the FIGO staging system for endometrial cancer. The neoplasm was divided into two groups based on mitotic activity. Patients underwent endouterine curettage, surgery therapy and, except one of them, chemotherapy. RESULTS: Two patients had low-grade ESS stage Ib and Ic. The other three had high-grade ESS, and were in stage IIIa. Treatment was surgery for all patients, and adjuvant chemotherapy for 4 out of 5. Both patients in stage I are alive, clinically free from the disease, 25 and 36 months after diagnosis. In stage III all patients died 14, 25 and 36 months after diagnosis. CONCLUSION: ESS is a rare uterine neoplasm. Histologic grade is the most important prognostic factor.

Surgical resection of a cerebral metastasis from cervical cancer: case report and review of the literature.

AIMS AND BACKGROUND: Central nervous system metastasis from cervical carcinoma is uncommon. CASE REPORT: We report the case of a 51-year-old woman who developed a solitary cerebral metastasis 29 months after radical hysterectomy with pelvic lymphadenectomy for a stage IB, grade III cervical cancer. The patient suddenly complained of headache, confusion and dizziness; she was submitted to emergency surgical resection of a 2 x 3 cm metastasis in the right frontal lobe. The postoperative course was uneventful and she completely recovered from her neurological deficit. Following surgery the patient underwent careful restaging. Massive bilateral involvement of the pelvic wall was diagnosed, and the patient received three courses of cisplatin-based chemotherapy. She developed liver and lung metastases and died 10 months later of progressive disseminated disease, without, however, any sign of recurrent or persistent cerebral involvement. CONCLUSION: Neurosurgical resection should be considered in cervical cancer patients with solitary brain metastasis in the absence of systemic disease.

Phase II study of cisplatin and vinorelbine as first-line chemotherapy in patients with carcinoma of the uterine cervix.

PURPOSE: To evaluate the activity and toxicity of the combination of cisplatin (80 mg/m2 day 1) and vinorelbine (25 mg/m2 days 1 and 8) in patients with carcinoma of the uterine cervix that has not been previously treated with chemotherapy. PATIENTS AND METHODS: Fifty patients with cervical cancer were enrolled onto this study (27 stage IB-III, 23 stage IVB-recurrent). A two-stage optimal Simon design was applied. Thirteen responders of 29 treated patients were required to proceed beyond the first stage, and 28 responders were needed overall. RESULTS: Hematologic toxicity was mild, with neutropenia being the most frequent side effect. Nonhematologic toxicity was frequent but never severe; one patient had grade 3 peripheral neurotoxicity. Objective responses were recorded for 32 patients (64%): 11 patients (22%) achieved a complete response (CR) and 21 patients (42%) achieved a partial response (PR). The response rate was 81.5% in patients with IB-III stage (25.9% CR rate) and 43.5% in patients with IVB-recurrent disease (17.4% CR rate). Responses were seen both in stage IVB patients (one CR and two PRs, for an overall rate of 37.5%) and in patients with recurrent disease (three CRs + four PRs, for an overall rate of 46.7%). CONCLUSION: The combination of cisplatin and vinorelbine is an active regimen in the treatment of patients with early-stage and advanced carcinoma of the uterine cervix. The hematologic and nonhematologic toxicity of this combination is mild.

Hypersensitivity reactions in ovarian cancer patients receiving paclitaxel.

OBJECTIVE: The aim of this study was to describe a rapid retreatment strategy in patients with paclitaxel hypersensitivity reactions. METHODS: A retrospective review of all patients receiving standard 3-hour infusion paclitaxel-based chemotherapy after proper premedication at the Department of Gynecologic Oncology, University of Bari between 1995 and 1998, was performed. All patients who developed hypersensitivity reactions to paclitaxel were identified and their treatment course and outcome were reviewed. A review of the literature on this subject is also presented. RESULTS: Eighty-six women were treated with 461 cycles of paclitaxel-based chemotherapy at our Unit. Twelve patients (14%) developed hypersensitivity reactions. All had received standard premedication consisting of corticosteroids and hystamine blockers. Hypersensitivity reactions consisted of isolated face flushes (3 patients), dyspnea and chest tightness (4 patients) or bronchospasm (5 patients). Eleven patients were rechallenged with the original paclitaxel solution starting at a slower rate after a second premedication with a double dosage of steroids. None of these patients had reactions in subsequent courses. Only one patient (the first of this series treated in February 1995), was retreated 5 days later under strict monitoring in intensive care unit. CONCLUSIONS: Retreatment with the original paclitaxel solution is safe in almost all patients with hypersensitivity reactions. The drug should be administered within the next 24 hours with a new premedication protocol.

[Chemotherapy in the treatment of ovarian carcinosarcoma]. / La chemioterapia nel trattamento del carcinosarcoma dell'ovaio.

Carcinosarcoma of the ovary is a rare neoplasm representing 1% of this organ malignancies. The disease appears almost exclusively in advanced stage having an unfavourable prognosis. Three patients affected by carcinosarcoma (MMMT) of the ovary admitted to our Operative Unit have been treated. All patients underwent surgery and subsequently chemotherapy. Two patients were affected by heterologous MMMT and were stage IV and IIIc respectively, the other one, affected by homologous MMMT, was stage IIIc. Stage IV patient was submitted to 6 cycles of CARBO + IFX + CDDP, second look and further 6 cycles of TAX. After 23 months she was submitted to colostomy for intestine occlusion. At the 35 months she died for cachexia and intestine occlusion. Stage IIIc heterologous patient was submitted to 6 cycles of CDDP + EPI + IFX + MESNA for 3 days; at 6 months from diagnosis she did not present any sign of disease. Stage IIIc homologous patient, affected by chronic renal insufficiency and submitted to dialysis, underwent 5 cycles of TAX and at 11 months from diagnosis presented partial response. Carcinosarcoma of the ovary, because of its rarity, and of the poor record of cases in the literature, is a much debated topic in particularitis complementary therapy. Opinions of the several authors are in contrast regarding the use of CHT + RT at the same time. Only RT after surgery does not seem to improve the survival of these patients. Personal experience, with the reported outlines, compared with survival, seems to confirm the use of CDDP and of IFX and to give new horizons to TAX, waiting for further findings.

Pure lipoma of the uterus in association with endometrial carcinoma.

Pure lipoma of the uterus is a very rare entity, with few cases described in the English literature. We report the case of a 71-year-old woman, with pure lipoma of the uterus and coexistent endometrial carcinoma and discuss the possible relationship between these pathologic entities.